One useful growth promoting factor for many types of animals is pantothenic acid, Vitamin (B.sub.5), and in a stable and preferred form is used as its double calcium salt, calcium pantothenate. As such it is used in large quantities in animal feeds, encapsulated in multivitamin capsules, and the like.
The classical procedure for the preparation of this valuable material is described by Stiller et al in the Journal of the American Chemical Society 62 1785 (1940) and involves the reaction of isobutyraldehyde with formalin in the presence of potassium carbonate. The aldol product is then purified by distillation and the racemic lactone is formed from the aldol by reaction with sodium bisulfite and potassium cyanide. The pantothenic acid is then formed by coupling the lactone with the ethyl ester of Beta-alanine.
Due to the commercial importance of pantothenic acid and its salts, particularly the calcium double salt, a great deal of research and development effort has gone into methods to improve purity and yields.
U.S. Pat. No. 2,780,645 describes a method for the preparation of calcium dl-pantothenate by reacting 2,4-dihydroxy-3,3-dimethylbutyronitrile with beta-alanine and calcium hydroxide in a lower aliphatic alcohol. U.S. Pat. No. 2,809,213 teaches the preparation of Calcium Pantothenate by reacting beta-alanine and alpha-hydroxy-beta, beta-dimethyl-gamma-butyrolactone (dl-pantolactone) in the presence of a secondary or tertiary amine and calcium metal.
Salts of pantothenic acid are prepared by a process which comprises contacting in a lower alkanol a complex of 1-Brucine and alpha-hydroxy-beta, beta-dimethyl-gamma-butyrolactone and an alkali or alkanine earth metal salt of beta-alanine in U.S. Pat. No. 3,150,175. U.S. Pat No. 3,564,052 teaches the preparation of calcium pantothenate by reacting beta-alanine and pantoyl lactone in the presence of calcium carbide.